Identification of Genetic Determinants and Enzymes Involved with the Amidation of Glutamic Acid Residues in the Peptidoglycan of <em>Staphylococcus aureus</em>

<div><p>The glutamic acid residues of the peptidoglycan of <em>Staphylococcus aureus</em> and many other bacteria become amidated by an as yet unknown mechanism. In this communication we describe the identification, in the genome of <em>S. aureus</em> strain COL, of two co-transcribed genes, <em>murT</em> and <em>gatD</em>, which are responsible for peptidoglycan amidation. MurT and GatD have sequence similarity to substrate-binding domains in Mur ligases (MurT) and to the catalytic domain in CobB/CobQ-like glutamine amidotransferases (GatD). The amidation of glutamate residues in the stem peptide of <em>S. aureus</em> peptidoglycan takes place in a later step than the cytoplasmic phase – presumably the lipid phase - of the biosynthesis of the <em>S. aureus</em> cell wall precursor. Inhibition of amidation caused reduced growth rate, reduced resistance to beta-lactam antibiotics and increased sensitivity to lysozyme which inhibited culture growth and caused degradation of the peptidoglycan.</p>